Smith Erica D, Kudlow Brian A, Frock Richard L, Kennedy Brian K
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Mech Ageing Dev. 2005 Apr;126(4):447-60. doi: 10.1016/j.mad.2004.10.006. Epub 2004 Dec 15.
Nuclear lamins were identified as core nuclear matrix constituents over 20 years ago. They have been ascribed structural roles such as maintaining nuclear integrity and assisting in nuclear envelope formation after mitosis, and have also been linked to nuclear activities including DNA replication and transcription. Recently, A-type lamin mutations have been linked to a variety of rare human diseases including muscular dystrophy, lipodystrophy, cardiomyopathy, neuropathy and progeroid syndromes (collectively termed laminopathies). Most diseases arise from dominant, missense mutations, leading to speculation as to how different mutations in the same gene can give rise to such a diverse set of diseases, some of which share little phenotypic overlap. Understanding the cellular dysfunctions that lead to laminopathies will almost certainly provide insight into specific roles of A-type lamins in nuclear organization. Here, we compare and contrast the LMNA mutations leading to laminopathies with emphasis on progerias, and discuss possible functional roles for A-type lamins in the maintenance of healthy tissues.
20多年前，核纤层蛋白被确定为核心核基质成分。它们被赋予了结构作用，如维持核完整性以及在有丝分裂后协助核膜形成，并且还与包括DNA复制和转录在内的核活动有关。最近，A型核纤层蛋白突变与多种罕见的人类疾病有关，包括肌肉萎缩症、脂肪营养不良、心肌病、神经病变和早衰综合征（统称为核纤层蛋白病）。大多数疾病源于显性错义突变，这引发了人们对于同一基因中的不同突变如何导致如此多样的一系列疾病的猜测，其中一些疾病几乎没有共同的表型重叠。了解导致核纤层蛋白病的细胞功能障碍几乎肯定会为A型核纤层蛋白在核组织中的特定作用提供见解。在此，我们比较并对比导致核纤层蛋白病的LMNA突变，重点关注早衰症，并讨论A型核纤层蛋白在维持健康组织中的可能功能作用。
